siRNA and RNA Interference
RNA interference (RNAi) is a phenomenon involving double-stranded (ds) RNA-dependent gene specific posttranscriptional silencing.
U.S. patent application Ser. No. 13/508,493, US Patent Applications publication Nos. 20060069056, 20100029746, 20100222409, 20110142917, 20120184597, 20120141378 and U.S. Pat. Nos. 7,825,099, 7,842,674, 7,910,566, 8,148,342, all to the assignee of the present application, relate to double-stranded RNA compounds and compositions useful in down-regulating a p53 gene and to use of such compounds and compositions for treating a patient suffering from or at risk for the development of a disease or a disorder associated with p53 gene expression.
U.S. Pat. Nos. 6,982,277, 7,008,956, 7,012,087, assigned to The Board of Trustees of the University of Illinois, relate to a method of reversibly inhibiting p53 for a sufficient time to allow normal cells in a host to recover from a stress-inducing event affecting the cell, to a method of reducing hair loss associated with a cancer therapy comprising administering a therapeutically effective dose of a reversible p53 inhibitor to a mammal in need thereof in conjunction with the cancer therapy; and to a method of reducing cell death in a mammal attributable to a stress-inducing event in a central nervous system affecting the cell, said method comprising administering to the mammal a therapeutically effective amount of a temporary p53 inhibitor to reversibly inhibit p53 activity.
US Application Publication Nos. 2010/0292301 and 2011/0112168, and PCT Patent Publication Nos. WO 2011/066475, WO 2011/084193, WO 2011/085056 and WO 2012/078536 to the assignee of the present invention and hereby incorporated by reference in their entirety, disclose nucleic acid sequences and modifications useful in generating dsRNA molecules.
US Application Publication Nos. 2011/0142917, 2011/0229557 and 2012/0141378 to the assignee of the present invention and hereby incorporated by reference in their entirety, disclose compositions and methods of use of double-stranded RNA compounds targeting a p53 gene.
Molecules, compositions, methods and kits useful in treating or attenuating a condition, a disease or a disorder associated with expression of a p53 gene and which exhibit at least one of increased bioavailability, improved biodistribution, increased serum circulation time, increased serum stability, decreased serum clearance, improved cellular uptake, reduced off target activity, reduced immunogenicity, improved endosomal release, improved specific delivery to target tissue or cell and increased knock down activity when compared to unmodified dsRNA counterparts are needed.